P646: EFFECTIVENESS AND SAFETY OF VENETOCLAX IN COMBINATION WITH RITUXIMAB (VENR) IN R/R CLL PATIENTS WITH OR WITHOUT RISK-ASSOCIATED GENETIC MARKERS – DATA FROM THE OBSERVATIONAL VERVE STUDY
Authors: I. Schwaner, H. Hebart, C. Losem, T. Wolff, K. Famulla, J. Huelsenbeck, B. Schmidt, T. Nösslinger, D. Rossi
Journal: HemaSphere (2022)

Background: Treatment with Venetoclax in combination with Rituximab (VenR) has shown promising efficacy and good tolerability in clinical trials1 However, there is limited real-world data on VenR in CLL patients with or without genetic markers, known to be associated with unfavorable outcomes. Aims: The non-interventional observational study VeRVe aims to investigate safety and effectiveness of VenR for treatment of CLL under real-world conditions in Germany, Austria, and Switzerland. In this analysis we focus on safety and effectiveness of VenR in CLL patients with or without TP53 mut and/or del(17p) as well as IGHV status. Methods: CLL patients included in this study required therapy and were eligible for VenR treatment according to local label2. Study documentation is possible at baseline, weekly during ramp-up, monthly until the end of month 6 and quarterly afterwards up to a maximum of 3 years. Response assessment can be documented at end of ramp-up, after 3, 12, 24 and 36 months. Results: At the time of analysis (November 4th, 2021), 100 patients were enrolled in the VenR arm of the VeRVe study and received at least one dose of Ven. 86 of them did also receive at least one dose of rituximab. 28 patients were female, 32 had aberrant TP53 (TP53 mut and/or del(17p)) and 40 were IGHV unmutated. TP53, del(17p) and IGHV status was unknown for 20, 18 and 42 patients, respectively. The median age was 72 y in the population with TP53 aberration and 71 y in the population with wild-type (wt) TP53. Within the TP53 aberrant vs the TP53 wt group 48% vs 67% had received 1, 48% vs 33% had received 2 or more prior lines of therapy. At least 1 comorbidity was reported for 85% of TP53 aberrant and 81% of TP53 wt patients. After 12 months of therapy, the best ORR was 88% in the total, 90% in the TP53 aberrant and 91% in the TP53 wt population. Thereby, CR/CRi was achieved in 54% of TP53 aberrant and 44% of TP53 wt patients. When subdivided according to IGHV status, the best ORR was 88% in IGHV mutated and 91% in IGHV unmutated patients. 29% of IGHV mutated and 62% of IGHV unmutated patients reached CR/CRi as best ORR within 12 months. However IGHV status was not documented for 42 patients. Estimated PFS-rates after 1 year were 88% in the total population and 86% and 90% in the TP53 aberrant and TP53 wt population, respectively (figure). Estimated OS-rates after 1 year were 90% in the total population, 93% in the TP53 aberrant population and 90% in the TP53 wt population. After a median observation time of 451 days (range 1-1016), CTCAE grade ≥3 AEs were reported in 57% (n=57) of all patients, 61% (n=20) in TP53 aberrant patients and 64% (n=27) in the TP53 wt patients. SAEs were reported in 36% (n=36) of all, 42% (n=14) in TP53 aberrant and 40% (n=17) in the TP53 wt patients. TLS occurred in 10 patients (10%) of the overall population. 2 of them where clinical TLS (both in the group TP53 wt). Image:Summary/Conclusion: In conclusion, patients with and without TP53 aberrations were comparable regarding age and burden of comorbidities, but in the group with TP53 aberrations slightly more patients had a high number of prior therapy lines. However, both populations responded to VenR treatment with comparably high best ORR, estimated PFS-rates and estimated OS-rates. This was also the case for IGHV mutated vs unmutated patients, however patient number was low for this analysis, because the IGHV status was often not documented in this real-world study. VenR treatment was well tolerated in the overall population and all subgroups and no new safety signals were detected.